Poloxamer 407, also known by the trademark Pluronic^® F127, is a water-soluble, non-ionic triblock copolymer that is made up of a hydrophobic residue of polyoxypropylene (POP) between the two hydrophilic units of polyoxyethylene (POE). Poloxamer 407-based hydrogels exhibit an interesting reversible thermal characteristic. That is, they are liquid at room temperature, but they assume a gel form when administered at body temperature, which makes them attractive candidates as pharmaceutical drug carriers. These systems have been widely investigated in the development of mucoadhesive formulations because they do not irritate the mucosal membranes. Based on these mucoadhesive properties, a simple administration into a specific compartment should maintain the required drug concentration in situ for a prolonged period of time, decreasing the necessary dosages and side effects. Their main limitations are their modest mechanical strength and, notwithstanding their bioadhesive properties, their tendency to succumb to rapid elimination in physiological media. Various technological approaches have been investigated in the attempt to modulate these properties. This review focuses on the application of poloxamer 407-based hydrogels for mucosal drug delivery with particular attention being paid to the latest published works.

Hydrogels are three-dimensional networks of hydrophilic polymers able to absorb and retain a considerable amount of water or biological fluid while maintaining their structure. Among these, thermo-sensitive hydrogels, characterized by a temperature-dependent sol–gel transition, have been massively used as drug delivery systems for the controlled release of various bioactives. Poloxamer 407 (P407) is an ABA-type triblock copolymer with a center block of hydrophobic polypropylene oxide (PPO) between two hydrophilic polyethyleneoxide (PEO) lateral chains. Due to its unique thermo-reversible gelation properties, P407 has been widely investigated as a temperature-responsive material. The gelation phenomenon of P407 aqueous solutions is reversible and characterized by a sol–gel transition temperature. The nanoencapsulation of drugs within biocompatible delivery systems dispersed in P407 hydrogels is a strategy used to increase the local residence time of various bioactives at the injection site. In this mini-review, the state of the art of the most important mixed systems made up of colloidal carriers localized within a P407 hydrogel will be provided in order to illustrate the possibility of obtaining a controlled release of the entrapped drugs and an increase in their therapeutic efficacy as a function of the biomaterial used.

Rutin is a flavone glycoside contained in many plants, and exhibits antioxidant, anti-inflammatory, anticancer, and wound-healing properties. The main disadvantage related to the use of this molecule for pharmaceutical application is its poor bioavailability, due to its low solubility in aqueous media. Poloxamer 407-hydrogels show interesting thermo-sensitive properties that make them attractive candidates as pharmaceutical formulations. The hydrophobic domains in the chemical structure of the copolymer, a polymer made up of two or more monomer species, are useful for retaining poorly water-soluble compounds. In this investigation various poloxamer 407-based hydrogels containing rutin were developed and characterized as a function of the drug concentration. In detail, the Turbiscan stability index, the micro- and dynamic rheological profiles and in vitro drug release were investigated and discussed. Rutin (either as a free powder or solubilized in ethanol) did not modify the stability or the rheological properties of these poloxamer 407-based hydrogels. The drug leakage was constant and prolonged for up to 72 h. The formulations described are expected to represent suitable systems for the in situ application of the bioactive as a consequence of their peculiar versatility.

In ophthalmology, developing effective drug delivery systems is crucial to overcome anatomical and physiological barriers, such as rapid tear turnover and blinking, which limit the efficacy of conventional formulations like eye drops. Poloxamers, especially the derivatives 407 (P407) and 188, are amphiphilic triblock copolymers characterized by an intriguing thermo-reversible behavior, making them ideal candidates for the development of in situ hydrogels for ocular applications. Various thermo-sensitive poloxamer-based hydrogels were designed to be easily instilled as liquids at room temperature, gelling promptly upon contact with the corneal surface. These systems promoted a controlled release of active compounds, significantly improving their adhesion to the ocular surface. This review discusses the most relevant scientific literature on the topic, with particular attention to studies published in recent years. The results demonstrated that poloxamer formulations are capable of overcoming typical ocular barriers, thereby increasing drug bioavailability. The intrinsic biocompatibility of poloxamers contributes to the safety and tolerability of the system. Furthermore, P407 showed additional wound healing features. The combination of biocompatibility and thermo-reversible behavior makes poloxamer-based hydrogels a promising platform for the development of innovative ocular drug delivery systems able to enhance therapeutic efficacy and patient comfort.

Ethosomes^® have been proposed as potential intra-articular drug delivery devices, in order to obtain a longer residence time of the delivered drug in the knee joint. To this aim, the conventional composition and preparation method were modified. Ethosomes^® were prepared by using a low ethanol concentration and carrying out a vesicle extrusion during the preparation. The modified composition did not affect the deformability of ethosomes^®, a typical feature of this colloidal vesicular topical carrier. The maintenance of sufficient deformability bodes well for an effective ethosome^® application in the treatment of joint pathologies because they should be able to go beyond the pores of the dense collagen II network. The investigated ethosomes^® were inserted in a three-dimensional network of thermo-sensitive poloxamer gel (EtoGel) to improve the residence time in the joint. Rheological experiments evidenced that EtoGel could allow an easy intra-articular injection at room temperature and hence transform itself in gel form at body temperature into the joint. Furthermore, EtoGel seemed to be able to support the knee joint during walking and running. In vitro studies demonstrated that the amount of used ethanol did not affect the viability of human chondrocytes and nanocarriers were also able to suitably interact with cells.